This invention relates to a noninvasive method and apparatus for determining cardiac output for an individual from CO.sub.2 gas expirograms and, more particularly, for determining both cardiac output and pulmonary arterial blood CO.sub.2 concentration of an individual.
Cardiac output, sometimes termed total cardiac output, is a well-known term for heart blood flowrate, i.e., the averaged cardiac blood flow per unit of time. Cardiac output for a healthy, adult male human being at rest is about 6000 ml/min, but cardiac output may range from about 1 l/min to about 20 l/min under other conditions (exercise, disease, etc.). Cardiac output is a highly useful measurement in assessing cardiac performance, diagnosing and determining the extent of cardiac and pulmonary disease, and monitoring the effect and effectiveness of treatment protocols involving, e.g., exercise or drugs.
Currently used techniques for determining cardiac output are invasive, i.e., methods requiring skilled personnel in which blood samples are withdrawn for analysis of blood gases, or in which an indicator medium is injected and monitored via blood sampling or catheterization. The dye-dilution technique, for example, requires venous catheterization, with injection proximate to the right atrium, and arterial catheterization with a catheter sufficient for withdrawal of dye-containing blood at a rate of 15-20 ml/min. Thermodilution, a widely used technique, requires right-sided catheterization to the pulmonary artery by a catheter/thermistor, with cold saline being injected near the right atrium to produce a dilution temperature curve useful for accurate determination of cardiac output.
Invasive cardiac output measurement techniques need to be used with great care since they involve a risk of adverse medical consequences if improperly executed. Likewise, the limitations of such invasive techniques are self-evident: they are complex procedures that require trained personnel and controlled conditions, e.g., a clinical environment, and they are not well suited for obtaining repeat measurements from unconfined individuals over extended periods of time. A recent study has raised questions about the safety of right heart catheterizations, i.e. pulmonary artery catheterizations, which are commonly used in invasive cardiac output measurement techniques as described above; see Connors, Jr. et al., J. Am. Med. Assn., (Sept. 18, 1996).
Several noninvasive techniques for determining cardiac output have been reported in the literature, but none has proven to be a simple, easily administered, reliable technique applicable generally to all individuals, i.e., healthy adults and children, as well as diseased and critical care patients; see, e.g., Conway, "Clinical Assessment of Cardiac Output", Europ. Heart J. 11:148-150 (1990).
Inert gas and CO.sub.2 rebreathing techniques, such as described by Stok et al., "Noninvasive Cardiac Output Measurement by Arterial Pulse Analysis Compared with Inert Gas Rebreathing", J. Appl. Physiol., 74:2687-2693 (1993), tend to raise mixed venous blood CO.sub.2 concentration which itself raises cardiac output during the measurement technique. Rebreathing techniques, moreover, are generally not suitable for critically ill patients, since patients are generally required to be cooperative and perform rapid, deep breathing maneuvers.
Stout et al., "Pulmonary Blood Flow Determined by Continuous Analysis of Pulmonary N.sub.2 O Exchange", J. Appl. Physiol. 38:913-918 (1975), describe a technique for measuring cardiac output by applying an idealized homogeneous lung model to multibreath analyses of soluble inert gas (N.sub.2 O) and insoluble inert gas (N.sub.2 or He) during artificial ventilation of anesthetized dogs breathing a gas mixture containing these components. Nielsen et al., "Precision and Accuracy of a Noninvasive Inert Gas Washing Method for Determination of Cardiac Output in Men", J. Appl. Physiol., 36:1560-1565 (1994), describes the application of the multibreath method of Stout et al. to healthy human beings under controlled ventilation at rest and during exercise, finding that the multibreath method was useful for determining cardiac output under exercise conditions but that an inert gas rebreathing method was more accurate at rest.
Stok et al., "Noninvasive Cardiac Output Measurement by Arterial Pulse Analysis Compared with Inert Gas Rebreathing", J. Appl. Physiol., 74:2687-2693 (1993), describe measurement of changes in cardiac output in healthy adult males by arterial pulse analysis, but this technique requires an initial determination or calibration of absolute cardiac output, e.g., by inert gas rebreathing or other potentially invasive methods.
Zenger et al. "Measurement of Cardiac Output by Automated Single-Breath Technique, and Comparison with Thermodilution and Fick Methods in Patients with Cardiac Disease", Am. J. Cardiol., 71:105-109 (1993), describe measurement of cardiac output from single breath measurements of acetylene gas, used as a tracer gas, but the technique requires controlled inhalation, breath-holding, constant rate exhalation by the individual being tested and administration of a tracer gas not normally present in the lung. This level of cooperation is unworkable with some patients for whom cardiac output measurements are nevertheless highly desirable, e.g., critically ill or unconscious patients.